Ch. 10 - Rethinking the Transgressive: A Call for “Pessimistic Activism” in Music Education

This essay asks the question: How are we to think of what Estelle Jorgensen has called “the transgressive” in music education today? My entry point to the question is the suggestion that the struggle against modes of music education that eulogize the status quo, against oppression and authoritarianism, against practices that exclude and intimidate students, has to take the form of “a struggle on two fronts” (Badiou). A struggle against imposed canonicities and obsolete approaches to music teaching but also a struggle against the emerging neoliberal appropriations of education, learning, and creativity. The chapter sketches a struggle-on-two-fronts perspective with regard to the following questions: (1) How are we to understand the call for being ‘open’ to students and their needs? What does it mean, today, to adopt a child-centric perspective in music education? (2) How should we think of the notion of “active” participation? (3) Should we simply accept an equation between informality and openness? The chapter concludes by arguing that, if an important task of education is to critically reconstruct, reinterpret, and re-examine “knowledge for the present and future,” as Estelle Jorgensen has put it, then our approach might need to take the form of a “pessimistic activism”. Invoking the Foucauldian notion of pessimistic activism, I wish to emphasize the need for persistent uncompromised working modes that foster experimentation and criticality on the basis of equality, in the knowledge that in the end, we can neither be sure that our efforts will lead to openness, nor that these efforts will not be cancelled and/or co-opted by the pervading neoliberal ethos

Bounding the inefficiency of compromise

Social networks on the Internet have seen an enormous growth recently and play a crucial role in different aspects of today's life. They have facilitated information dissemination in ways that have been beneficial for their users but they are often used strategically in order to spread information that only serves the objectives of particular users. These properties have inspired a revision of classical opinion formation models from sociology using game-theoretic notions and tools. We follow the same modeling approach, focusing on scenarios where the opinion expressed by each user is a compromise between her internal belief and the opinions of a small number of neighbors among her social acquaintances. We formulate simple games that capture this behavior and quantify the inefficiency of equilibria using the well-known notion of the price of anarchy. Our results indicate that compromise comes at a cost that strongly depends on the neighborhood size

Bounding the Inefficiency of Compromise in Opinion Formation

Social networks on the Internet have seen an enormous growth recently and play a crucial role in different aspects of today’s life. They have facilitated information dissemination in ways that have been beneficial for their users but they are often used strategically in order to spread information that only serves the objectives of particular users. These properties have inspired a revision of classical opinion formation models from sociology using game-theoretic notions and tools. We follow the same modeling approach, focusing on scenarios where the opinion expressed by each user is a compromise between her internal belief and the opinions of a small number of neighbors among her social acquaintances. We formulate simple games that capture this behavior and quantify the inefficiency of equilibria using the well-known notion of the price of anarchy. Our results indicate that compromise comes at a cost that strongly depends on the neighborhood size

Side-Chain Modified [^99mTc]Tc-DT1 Mimics:A Comparative Study in NTS₁R-Positive Models

Radiolabeled neurotensin analogs have been developed as candidates for theranostic use against neurotensin subtype 1 receptor (NTS1R)-expressing cancer. However, their fast degradation by two major peptidases, neprilysin (NEP) and angiotensin-converting enzyme (ACE), has hitherto limited clinical success. We have recently shown that palmitoylation at the ε-amine of Lys7 in [99mTc]Tc-[Lys7]DT1 (DT1, N4-Gly-Arg-Arg-Pro-Tyr-Ile-Leu-OH, N4 = 6-(carboxy)-1,4,8,11-tetraazaundecane) led to the fully stabilized [99mTc]Tc-DT9 analog, displaying high uptake in human pancreatic cancer AsPC-1 xenografts but unfavorable pharmacokinetics in mice. Aiming to improve the in vivo stability of [99mTc]Tc-DT1 without compromising pharmacokinetics, we now introduce three new [99mTc]Tc-DT1 mimics, carrying different pendant groups at the ε-amine of Lys7: MPBA (4-(4-methylphenyl)butyric acid)—[99mTc]Tc-DT10; MPBA via a PEG4-linker—[99mTc]Tc-DT11; or a hydrophilic PEG6 chain—[99mTc]Tc-DT12. The impact of these modifications on receptor affinity and internalization was studied in NTS1R-positive cells. The effects on stability and AsPC-1 tumor uptake were assessed in mice without or during NEP/ACE inhibition. Unlike [99mTc]Tc-DT10, the longer-chain modified [99mTc]Tc-DT11 and [99mTc]Tc-DT12 were significantly stabilized in vivo, resulting in markedly improved tumor uptake compared to [99mTc]Tc-DT1. [99mTc]Tc-DT11 was found to achieve the highest AsPC-1 tumor values and good pharmacokinetics, either without or during NEP inhibition, qualifying for further validation in patients with NTS1R-positive tumors using SPECT/CT.</p

The Distortion of Distributed Facility Location

We study the distributed facility location problem, where a set of agents with positions on the line of real numbers are partitioned into disjoint districts, and the goal is to choose a point to satisfy certain criteria, such as optimize an objective function or avoid strategic behavior. A mechanism in our distributed setting works in two steps: For each district it chooses a point that is representative of the positions reported by the agents in the district, and then decides one of these representative points as the final output. We consider two classes of mechanisms: Unrestricted mechanisms which assume that the agents directly provide their true positions as input, and strategyproof mechanisms which deal with strategic agents and aim to incentivize them to truthfully report their positions. For both classes, we show tight bounds on the best possible approximation in terms of several minimization social objectives, including the well-known average social cost (average total distance of agents from the chosen point) and max cost (maximum distance among all agents from the chosen point), as well as other fairness-inspired objectives that are tailor-made for the distributed setting, in particular, the max-of-average and the average-of-max

Key-protease inhibition regimens promote tumor targeting of neurotensin radioligands

Neurotensin subtype 1 receptors (NTS1R) represent attractive molecular targets for directing radiolabeled neurotensin (NT) analogs to tumor lesions for diagnostic and therapeutic purposes. This approach has been largely undermined by the rapid in vivo degradation of linear NT-based radioligands. Herein, we aim to increase the tumor targeting of three99mTc-labeled NT analogs by the in-situ inhibition of two key proteases involved in their catabolism. DT1 ([N4- Gly7]NT(7-13)), DT5 ([N4-βAla7,Dab9]NT(7-13)), and DT6 ([N4-βAla7,Dab9,Tle12]]NT(7-13)) were labeled with99mTc. Their profiles were investigated in NTS1R-positive colon adenocarcinoma WiDr cells and mice treated or not with the neprilysin (NEP)-inhibitor phosphoramidon (PA) and/or the angiotensin converting enzyme (ACE)-inhibitor lisinopril (Lis). Structural modifications led to the partial stabilization of99mTc-DT6 in peripheral mice blood (55.1 ± 3.9% intact), whereas99mTc-D

One step closer to clinical translation: Enhanced tumor targeting of [99mTc]Tc-DB4 and [111In]In-SG4 in mice treated with entresto

Background: Peptide radioligands may serve as radionuclide carriers to tumor sites overexpressing their cognate receptor for diagnostic or therapeutic purposes. Treatment of mice with the neprilysin (NEP)-inhibit

Not All Strangers Are the Same: The Impact of Tolerance in Schelling Games

Schelling's famous model of segregation assumes agents of different types, who would like to be located in neighborhoods having at least a certain fraction of agents of the same type. We consider natural generalizations that allow for the possibility of agents being tolerant towards other agents, even if they are not of the same type. In particular, we consider an ordering of the types, and make the realistic assumption that the agents are in principle more tolerant towards agents of types that are closer to their own according to the ordering. Based on this, we study the strategic games induced when the agents aim to maximize their utility for a variety of tolerance levels. We provide a collection of results about the existence of equilibria, and their quality in terms of social welfare